This protocol is designed to study the techniques needed to develop gene therapy or other treatments for certain inherited immune system diseases.

Healthy normal volunteers between 18 and 65 years of age and patients with chronic granulomatous disease (CGD), X-linked severe combined immune deficiency (X-SCID), leukocyte adhesion deficiency (LAD), interferon gamma receptor deficiency (IGR-deficiency) or other inherited diseases affecting precursor blood cells bone marrow cells that generate blood cells may be eligible for this study. Patients who have had repeated severe infections possibly due to an inherited blood cell abnormality may also participate. Candidates will be screened with a medical history, physical examination and blood tests.

Patients with an active infection will be hospitalized during this study. Uninfected participants will be seen as outpatients at the NIH Clinical Center. Participants will have the following procedures:

G-CSF administration All participants will have daily injections of granulocyte-colony stimulating factor (G-CSF). This drug is a genetically engineered hormone that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream. The injections are given under the skin in the arm or leg, using a very small needle. Patients will have injections for 6 or 7 days, normal volunteers for 5. A small blood sample will be drawn each day of the injections to monitor white cell counts and changes in the number of blood cell precursors. (Smaller children and all children under 10 years of age may have blood drawn on alternate days or less to reduce the number of needle sticks and the amount of blood taken.). Larger blood draws will be taken on days 6 and/or 7 for patients and on days 5 and/or 6 for normal volunteers.

Leukapheresis This procedure for collecting larger numbers of circulating blood precursor cells is optional and may take the place of the larger blood draw described above. Patients 5 years old or older may have leukapheresis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The desired cells are then removed and the rest of the blood is returned to the body, either through the same needle or through a second one placed in the other arm. The cells obtained will be used to purify blood precursors for growing in culture and to examine the ability to transfer new genes into these precursor cells. For patients whose arm veins are too scarred to for needle placement, a vein in the groin area (femoral vein) may be used instead.

Bone marrow aspiration This procedure for obtaining a bone marrow sample is optional. Normal volunteers who agree to the procedure may undergo aspiration up to three times. The hip area is anesthetized and a small sample of bone marrow is drawn through a special needle inserted in the hipbone. The first aspiration is done on a day before the G-CSF injections are started; the second is done soon after the last injection (day 6 or 7), and the third is done from 7 to 10 days after the last injection.

Repeat blood tests At day 6 or 7 some of the blood tests done at the beginning of the study will be repeated to check blood counts and liver and kidney function.

Four months or more after the end of the study, participants will be asked to repeat the entire procedure to examine the effects of two cycles of G-CSF mobilization in the same individual. This second cycle is optional.

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

1. To efficiently and safely mobilize to the peripheral blood and apheresis collect CD34+ PBSC patients with any inherited primary immune deficiency (PID) where PBSC from these patients may be designated entirely or in part for future clinical t... [ Time Frame: This will be happening throughout length of study. ] [ Designated as safety issue: No ]

2. To efficiently and safely mobilize to the peripheral blood and apheresis collect CD34+ PBSC from healthy volunteers, which will be designated entirely for laboratory research. [ Time Frame: This will be happening throughout length of study. ] [ Designated as safety issue: No ]

3. To efficiently and safely mobilize to the peripheral blood and apheresis collect CD34+ PBSC from healthy sibling or other related donor of patients with PID in need of an allogeneic stem cell transplant where PBSC from these subjects are desi... [ Time Frame: This will be happening throughout length of study. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

4. To efficiently and safely collect peripheral blood mononuclear cells and granulocytes from subjects with chronic granulomatous disease or healthy donors for preclinical cell therapy studies, following either no stimulation, G-CSF or dexametha... [ Time Frame: This will be happening throughout length of study ] [ Designated as safety issue: No ]

5. To perform a bone marrow harvest by needle aspiration using standard of medical care methods from patients with PID in sufficient quantity cryopreserved in CC DTM to serve as the source of autologous HSC for gene transfer ex vivo transduction... [ Time Frame: This will be happening throughout length of study ] [ Designated as safety issue: No ]

6. To perform a bone marrow harvest by needle aspiration using standard of medical care methods from healthy sibling or other related donor of patients with PID in sufficient quantity cryopreserved in CC DTM to serve as the source of allogeneic ... [ Time Frame: This will be happening throughout length of study ] [ Designated as safety issue: No ]

Patients (Patients with a genetically defined PID or clinical history consistent with PID)

Patients will have a genetically defined PID or have a clinical history of recurrent infections or other problems suggestive of PID, must be 2-70 years of age,

Is at least 10 kilograms body weight.

Some patients may have active bacterial or fungal infection at the time of study entry.

Preserved renal function (creatinine < 2.5 mg/dL; < 3+ proteinuria); preserved hepatic function (bilirubin < 2.0 mg/dl); preserved hematologic function (WBC greater than or equal to1000/mm3;granulocytes greater than or equal to 500/mm3; platelets greater than or equal to 100,000; hematocrit greater than or equal to 25). Of note, patients with PID often have associated chronic thrombocytopenia. Patients with stable chronic thrombocytopenia will be eligible for collection, at the investigator s discretion, with the caveat that patients with platelet count < 40,000 the day prior to collection will be transfused with platelets on the morning of collection. Platelets may also be given to these patients following the collection if medically indicated..

Patients of childbearing potential may be entered if using effective contraception and having a negative serum pregnancy test within one week of beginning G-CSF administration.

Patients may remain on their regimen of prophylactic treatments as deemed necessary by the investigator.

Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test are excluded.

Must be negative by routine blood donor eligibility testing criteria including tests for syphilis (RPR) and TTV Donor Transplant Panel testing (list is modified periodically, but may include hepatitis B and C, HIV and HTLV, T. cruzi).

XSCID patients do not make antibodies and false positives may occur because they receive periodic infusions of pooled donations of IVIG. We have observed positive anti-HBc testing in these patients. If this occurs, more specific DNA or antigen testing will be done and must be negative.

Autologous HSC Transplant patients may be positive for Hepatitis B and C if the investigator deems it necessary to be collected and used as a safety back-up

If in the opinion of the investigator participation in this study places the healthy volunteer or donor at undue risk.

These same exclusion criteria applies for subjects with PID participating in mononuclear cells/granulocytes collection for research.

Patients or Healthy Donors being considered for clinical scale bone marrow harvesting

Who are unable to lie prone during the bone marrow harvesting procedure.

Who are unable to tolerate general anesthesia during the bone marrow harvesting procedure.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00001405